Solid Tumor, AdultPhase 1NCT05840510
Adagrasib in Combination With Nab-Sirolimus in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer With a KRAS G12C Mutation (KRYSTAL -19)
A Phase 1 study testing Adagrasib and nab-Sirolimus in people with Solid Tumor, Adult and NSCLC, run by Mirati Therapeutics Inc. at 3 sites in United States.
Trial summary
This study will evaluate the safety, MTD and/or RP2D, PK, and clinical activity of the combination of adagrasib with nab-sirolimus in patients with advanced solid tumors/NSCLC with a KRAS G12C mutation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Adult, NSCLC, Advanced Cancer
- What is being tested?
- Adagrasib and nab-Sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 3 sitesUnited States
- Study dates
- 7 Aug 2023to 27 Dec 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of solid tumor malignancy (Phase 1) or NSCLC (Phase 2) with KRAS G12C mutation
- Unresectable or metastatic disease
- No available treatment with curative intent
- Adequate organ function
- Measurable disease per RECIST 1.1.
Who cannot join
- History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow
- History of interstitial lung disease or radiation pneumonitis requiring steroid treatment, or any evidence of clinically active interstitial lung disease or pneumonitis
- Cardiac abnormalities
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Local Institution - 019-104
Cleveland, Ohio, 44121
Local Institution - 019-102
Houston, Texas, 77030-4000
Local Institution - 019-101
Nashville, Tennessee, 37203
About this study
Official title: A Phase 1/2 Trial of Adagrasib in Combination With Nab-Sirolimus in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer With a KRAS G12C Mutation
This study will evaluate the safety, MTD and/or RP2D, PK, and clinical activity of the combination of adagrasib with nab-sirolimus in patients with advanced solid tumors/NSCLC with a KRAS G12C mutation.
Read the detailed description
This study will evaluate the safety and tolerability and clinical activity of adagrasib in combination with nab-sirolimus in patients with advanced solid tumors harboring a KRAS G12C mutation.
The Phase 1 portion will enroll advanced solid tumors to establish the maximum tolerated dose (MTD) and/or to identify recommended Phase 2 combinatorial doses. The Phase 2 portion will enroll patients with NSCLC to further evaluate the safety/tolerability and clinical activity.
Adagrasib is an orally available small molecule inhibitor of KRAS G12C. nab-Sirolimus is a nanoparticle albumin-bound (nab) form of sirolimus, and sirolimus is an inhibitor of mechanistic target of rapamycin kinase (mTOR, previously known as mammalian target of rapamycin).
- Conditions
- Solid Tumor, Adult, NSCLC, Advanced Cancer, Metastatic Cancer, Malignant Neoplastic Disease
- Being tested
- Adagrasib, nab-Sirolimus
- Keywords
- KRAS, NSCLC, Adagrasib, KRAS G12C, mTOR, nab-sirolimus, Fyarro, ABI-009
- Medical subject headings
- Neoplasm Metastasis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdagrasibDrug
Also called MRTX849, Krazati
KRAS G12C inhibitor
nab-SirolimusDrug
Also called ABI -009, Fyarro
mTOR inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation and Clinical Efficacy | Experimental | Dose escalation of adagrasib and nab-Sirolimus to determine maximum tolerated dose in combination and evaluate the clinical efficacy of adagrasib in combination with nab-sirolimus in patients with solid tumors (Phase 1) and NSCLC (Phase 2) harboring a KRAS G12C mutation Receives: Drug: Adagrasib; Drug: nab-Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Safety and tolerability in the study population.
Safety characterized by the following, as noted from first dose of study treatment to 28 days after last dose of study treatment:
- Type, incidence, severity, timing, seriousness and relationship to study treatment of Adverse Events
- Laboratory abnormalities, as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment
- Number of patients modifying or discontinuing study treatment due to an AE
Measured: 30 months
Phase 1: Maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D)
Evaluate safety and assess number of patients with dose-limiting toxicity to determine the MTD/RP2D.
Measured: 30 months
Phase 2: Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) (Phase 2)
ORR evaluation of subjects treated with adagrasib in combination with nab-sirolimus in patients with NSCLC with KRAS G12C mutation (Study Population) will be completed. Objective response is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from first dose of study treatment until last dose of study treatment.
Measured: 30 months
Secondary outcomes (7)
Area under the plasma concentration versus time curve (AUC)
AUC - nab-sirolimus and adagrasib
Measured: Up to 7 days
Time to achieve maximal plasma concentration
Tmax - nab-sirolimus and adagrasib
Measured: Up to 1 days
Maximum observed plasma concentration
Cmax - nab-sirolimus and adagrasib
Measured: Up to 1 days
Terminal elimination half-life
t1/2 - nab-sirolimus
Measured: Up to 7 days
Phase 1 and 2: Evaluate efficacy endpoints characterized by overall survival, progression-free survival, and duration of response in the study population.
- Overall survival is defined as time from date of randomization to date of death due to any cause.
- Progression-free survival is defined as the time from randomization to the date of Progressive Disease (PD) or death due to any cause,whichever occurs first.
- Duration of response defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either PD or death due to any cause, whichever occurs first.
Measured: 30 months
Phase 1: Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
ORR evaluation of subjects treated with adagrasib in combination with nab-sirolimus in patients with advanced solid tumors and NSCLC with KRAS G12C mutation (Study Population) will be completed. Objective response is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from first dose of study treatment until last dose of study treatment.
Measured: 30 months
Phase 2: Safety and tolerability in the study population.
Safety characterized by the following, as noted from first dose of study treatment to 28 days after last dose of study treatment:
- Type, incidence, severity, timing, seriousness and relationship to study treatment of Adverse Events
- Laboratory abnormalities, as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment
- Number of patients modifying or discontinuing study treatment due to an AE,
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2023
- Study start7 Aug 2023
- Primary completion27 Dec 2024
- Study completion27 Dec 2024
Why it stopped: Business objectives have changed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumor, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mirati Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Aadi Bioscience, Inc.
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05840510
- Sponsor's protocol ID
- CA239-0011
- Other IDs
- CA239-0011, 849-019
- Status last verified
- Apr 2025
- First submitted
- 12 Apr 2023
- Last updated
- 25 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Trial of Adagrasib in Combination With Nab-Sirolimus in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer With a KRAS G12C Mutation
- ClinicalTrials.gov ID
- NCT05840510
- Acronym / sponsor ID
- CA239-0011
- Conditions
- Solid Tumor, Adult, NSCLC, Advanced Cancer, Metastatic Cancer, Malignant Neoplastic Disease
- Keywords
- KRAS, NSCLC, Adagrasib, KRAS G12C, mTOR, nab-sirolimus, Fyarro, ABI-009
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business objectives have changed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Mirati Therapeutics Inc.Industry (pharma, biotech, devices)
- Collaborators
- Aadi Bioscience, Inc.
- Study start
- 7 Aug 2023 (actual)
- Primary completion
- 27 Dec 2024 (actual)
- Study completion
- 27 Dec 2024 (actual)
- First posted
- 3 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety, MTD and/or RP2D, PK, and clinical activity of the combination of adagrasib with nab-sirolimus in patients with advanced solid tumors/NSCLC with a KRAS G12C mutation.
Detailed description
This study will evaluate the safety and tolerability and clinical activity of adagrasib in combination with nab-sirolimus in patients with advanced solid tumors harboring a KRAS G12C mutation.
The Phase 1 portion will enroll advanced solid tumors to establish the maximum tolerated dose (MTD) and/or to identify recommended Phase 2 combinatorial doses. The Phase 2 portion will enroll patients with NSCLC to further evaluate the safety/tolerability and clinical activity.
Adagrasib is an orally available small molecule inhibitor of KRAS G12C. nab-Sirolimus is a nanoparticle albumin-bound (nab) form of sirolimus, and sirolimus is an inhibitor of mechanistic target of rapamycin kinase (mTOR, previously known as mammalian target of rapamycin).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation and Clinical Efficacy | Experimental | Drug: Adagrasib, Drug: nab-SirolimusDose escalation of adagrasib and nab-Sirolimus to determine maximum tolerated dose in combination and evaluate the clinical efficacy of adagrasib in combination with nab-sirolimus in patients with solid tumors (Phase 1) and NSCLC (Phase 2) harboring a KRAS G12C mutation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Histologically confirmed diagnosis of solid tumor malignancy (Phase 1) or NSCLC (Phase 2) with KRAS G12C mutation
- Unresectable or metastatic disease
- No available treatment with curative intent
- Adequate organ function
- Measurable disease per RECIST 1.1.
Key exclusion criteria (3 listed)
- History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow
- History of interstitial lung disease or radiation pneumonitis requiring steroid treatment, or any evidence of clinically active interstitial lung disease or pneumonitis
- Cardiac abnormalities
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdagrasibAlso: MRTX849, KrazatiKRAS G12C inhibitor | Drug | Dose Escalation and Clinical Efficacy |
| nab-SirolimusAlso: ABI -009, FyarromTOR inhibitor | Drug | Dose Escalation and Clinical Efficacy |
Primary outcome
Phase 1: Safety and tolerability in the study population.
Time frame: 30 months
Safety characterized by the following, as noted from first dose of study treatment to 28 days after last dose of study treatment: 1. Type, incidence, severity, timing, seriousness and relationship to study treatment of Adverse Events 2. Laboratory abnormalities, as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment 3. Number of patients modifying or discontinuing study treatment due to an AE
Phase 1: Maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D)
Time frame: 30 months
Evaluate safety and assess number of patients with dose-limiting toxicity to determine the MTD/RP2D.
Phase 2: Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) (Phase 2)
Time frame: 30 months
ORR evaluation of subjects treated with adagrasib in combination with nab-sirolimus in patients with NSCLC with KRAS G12C mutation (Study Population) will be completed. Objective response is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from first dose of study treatment until last dose of study treatment.
7 secondary outcomes
Area under the plasma concentration versus time curve (AUC)
Time frame: Up to 7 days
Time to achieve maximal plasma concentration
Time frame: Up to 1 days
Maximum observed plasma concentration
Time frame: Up to 1 days
Terminal elimination half-life
Time frame: Up to 7 days
Phase 1 and 2: Evaluate efficacy endpoints characterized by overall survival, progression-free survival, and duration of response in the study population.
Time frame: 30 months
Phase 1: Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Time frame: 30 months
Phase 2: Safety and tolerability in the study population.
Time frame: 30 months
Results and safety
The study was stopped early (reason given: Business objectives have changed). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2025.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Adagrasib and nab-Sirolimus in people with Solid Tumor, Adult and NSCLC, run by Mirati Therapeutics Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business objectives have changed). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Safety and tolerability in the study population. (time frame: 30 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2025.